Physicians around the world have used naturally occurring substances to decrease pain for hundreds of years. The two main ingredients used for pain relief are capsaicin and menthol. These active ingredients most commonly are found in pain-relieving creams and gels, but also can be applied with roll-ons or sprays. Capsaicin is the hot substance in chili peppers, while menthol is the cool substance in peppermint oil. Menthol is a common ingredient in many products we use daily, such as toothpaste, chewing gum and mouthwash. When applied to the skin, these ingredients are used as "topical analgesics." This means they decrease the sensation of pain when applied to the skin.

Mechanism of Action

Traditionally, it was thought that these substances reduced pain through a "counter-irritant" mechanism. It's important to remember that the perception of pain essentially is a message sent from parts of the body into the brain, so we feel the sensation of pain. The counter-irritant theory was based on the active ingredient actually "irritating" the skin to create a reaction that cancelled out the pain signal before it reached the brain. Essentially, this skin irritation would stimulate certain nerve fibers (larger-sized nerve fibers) that would send more information than the smaller-sized nerve fibers carrying the pain signals, essentially blocking the pain signal from reaching the brain. This is known as the gate-control theory and is a commonly held view of pain relief.

Classic research on menthol has shown that topical application will increase cutaneous blood flow and increase the pain threshold (tolerance to pain). This research supported the theory that menthol, in particular, acted as a "counter-irritant."

Recent exciting research, however, has shed some doubt on the counter-irritant function as the only mechanism of pain relief for topical analgesics containing capsaicin and menthol. Researchers have shown that menthol, in particular, actually might stimulate the smaller-diameter nerve fibers, rather than the larger-diameter fibers. While researchers aren't ready to totally discount the counter-irritant mechanism and theory, these new discoveries might help rethink how chronic pain patients are treated and offer even better options for helping patients with all types of pain.

Clinicians have noted that many patients with chronic pain also have temperature sensitivities. Researchers have shown there is, in fact, a link between chronic pain and temperature ("thermal") sensation, specifically because these two perceptions share similar paths to the brain in the spinal cord. Therefore, when local pain becomes chronic (lasting more than one month), the pain becomes "centralized" in the central nervous system, meaning the perceptions we have of pain are controlled more by the brain than by the actual site of the pain itself.

Scientists first discovered specialized protein receptors in nerves that are sensitive to capsaicin and create the sensation of warmth in our brain. These receptors are called "transient receptor protein" or "TRP" channels, and they help give us our sense of temperature. Therefore, they are known as "thermosensitive" receptors. The first of these specialized receptors was discovered for capsaicin: the TRPV1 or "vanilloid" receptor, which is responsible for our sense of warmth.